title: Regulation of embryonic neurotransmitter and tyrosine hydroxylase protein levels by ascorbic acid.
abstract: METHODS
  Ascorbic acid (ascorbate) is required to recycle tetrahydrobiopterin, which is necessary for neurotransmitter synthesis by the rate-limiting enzymes tyrosine and tryptophan hydroxylases. We sought to determine whether ascorbate might regulate embryonic brain cortex monoamine synthesis utilizing transgenic mouse models with varying intracellular ascorbate levels.
  
  
  RESULTS
  In embryos lacking the sodium-dependent vitamin C transporter 2 (SVCT2), very low levels of brain ascorbate decreased cortex levels of norepinephrine and dopamine by approximately 33%, but had no effect on cortex serotonin or its metabolite, 5-hydroxyindole acetic acid. This decrease in ascorbate also led to a decrease in protein levels of tyrosine hydroxylase, but not of tryptophan hydroxylase. Increased cortex ascorbate in embryos carrying extra copies of the SVCT2 resulted in increased levels of dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), as well as serotonin and 5-hydroxyindole acetic acid.
  
  
  CONCLUSIONS
  The dependence of embryonic brain cortex neurotransmitter synthesis and tyrosine hydroxylase expression on intracellular ascorbate emphasizes the importance of receiving adequate ascorbate during development.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University, 2213 Garland Avenue, 7465 MRBIV, Nashville, TN 37232-0465, USA. Electronic address: Elizabeth.meredith@Vanderbilt.edu.
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Meredith
authors.forename: James M
authors.initials: JM
authors.lastname: May
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000032:analysis / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002540:Cerebral Cortex / Q000737:chemistry / Q000196:embryology* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D060347:Sodium-Coupled Vitamin C Transporters / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D002395:Catecholamines; C555165:Slc23a2 protein, mouse; D060347:Sodium-Coupled Vitamin C Transporters; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D001205:Ascorbic Acid; D004298:Dopamine; D009638:Norepinephrine
keywords: 3,4-dihydroxyphenylacetic acid; AA; Ascorbic acid; DOPAC; Development; Neurotransmitter; SVCT2; Sodium-dependent vitamin C transporter 2; Tyrosine hydroxylase; WT; ascorbic acid; gulo; gulonolactone oxidase; sodium-dependent vitamin C transporter 2; wild-type